Burkholderia cepacia (formerly known as Pseudomonas cepacia) is an aerobic gram-negative bacillus commonly found throughout the environment and as a phytopathogen causing soft rot in onions (1) (the numbers in brackets used throught this disclosure refer to the articles identified in the section entitled "References" provided later in the specification). Over the past decade, however, strains have been encountered with increasing frequency which cause opportunistic infections in humans, most notably in cystic fibrosis (CF) patients leading to an increase in morbidity and mortality (12, 38). Among non-CF patients, extrapulmonary nosocomial infections in compromised individuals have more recently been reported (21).
Although the mechanism of virulence of B. cepacia has not been elucidated (20), isolates from CF patients have been shown to adhere to mucin (26) and buccal epithelial cells (27). There may also be a correlation between the source of B. cepacia isolates (e.g. environmental, CF-associated epidemic and non-epidemic isolates) and the particular class of pili expressed (9). In addition, epidemic foci in Canada have been found associated with a suite of enzyme alleles characterized as electrophore type 12 (ET12) (Johnson et al., 1994).
The implications of being colonized with B. cepacia are a growing concern in the CF community and markers of strain virulence are eagerly sought. Enhanced transmissibility and virulence appear to be strain dependent and epidemic lineages are being defined anecdotally and genetically (10, 13, 17, 33, 34, 35, 36). To date, studies have indicated cross-infection between patients (10, 17, 25, 31) and nosocomial acquisition (19) as important parameters of transmission.
In attempts to limit the spread of B. cepacia, many clinical centres now segregate colonized and non-colonized CF patients. This has proved to be successful but is limited by the social contacts between patients outside the hospital setting that is the norm for CF patient groups, especially adults (10, 17, 31), and by the likelihood that not all B. cepacia strains are virulent.
Many studies involving B. cepacia have focused on its truly extraordinary potential to metabolize a wide variety of organic compounds. It is currently thought that this metabolic versatility may, in part, be the result of the genomic complexity (24) comprising three chromosomes and a large plasmid with possibly a large number of insertion sequence (IS) elements (7, 15). IS elements have the ability to promote genomic rearrangement, recruit foreign genes and cause insertional gene activation. Indeed, most of the IS elements in B. cepacia have been identified by observing these features (16) that dramatically modify the activity of isolates (8). It is conceivable that they may act genetically to increase transmissibility and pathogenicity of certain strains of B. cepacia.
The inventors named in the present application originally identified the strains obtained by Govan et al. in 1993 and by themselves (13, 25), from the United Kingdom and Canada respectively, as having an identical enzyme electrophoretic allotype (ET12), the first direct evidence that the anecdotal association of Canadian B. cepacia strains currently endemic in Ontario and those causing an epidemic in the United Kingdom were the same.
However, while B. cepacia has recently been the subject of much research, not a great deal of information is available about why some strains are particularly virulent, and to what factors the difference in virulence can be attributed. In practice, there is a need for a simple diagnostic way of identifying particularly virulent isolates of B. cepacia so that carrier patients can be suitably treated and non-carrier patients can be protected.